Citation: Yan-Jiao Lu, Li-Fen Ning, Yue Leng, Zi-Han Hu, Chun-Hua Chen, Gui-Fa Su, Dong-Liang Mo. Synthesis of angularly fused tricyclic isoxazolines through cycloaddition of N-cyclopentenyl nitrones with nitroalkenes[J]. Chinese Chemical Letters, ;2026, 37(11): 112370. doi: 10.1016/j.cclet.2026.112370 shu

Synthesis of angularly fused tricyclic isoxazolines through cycloaddition of N-cyclopentenyl nitrones with nitroalkenes

Yan-Jiao Lu ^{a, 1} ,
Li-Fen Ning ^{a, 1} ,
Yue Leng ^a ,
Zi-Han Hu ^a ,
Chun-Hua Chen ^{b, *,} ,
Gui-Fa Su ^{a, *,} ,
Dong-Liang Mo ^{a, *,}

a.
Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, University Engineering Research Center for Chemistry of Characteristic Medicinal Resources (Guangxi), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China
b.
Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission; Guangxi Key Laboratory of Chemistry and Engineering of Forest Products; Engineering Research Center of Low-carbon and High-quality Utilization of Forest Biomass, University of Guangxi; School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China

ChenChunHua@gxmzu.edu.cn

gfysglgx@163.com

moeastlight@mailbox.gxnu.edu.cn

Received Date: 3 September 2025
Revised Date: 29 December 2025
Accepted Date: 6 January 2026
Available Online: 7 January 2026

Figures(7)

Owing to the strong rigidity and difficult diastereoselectivity control, the construction of angularly fused tricyclic scaffolds containing multiple contiguous stereocenters has become one of the most challenging research topics. Herein, we report an efficient method to prepare various angularly fused 6-5-5 tricyclic isoxazolines containing five contiguous stereocenters in good yields with high diastereoselectivity from N-cyclopentenyl nitrones and nitroalkenes under mild reaction conditions. Mechanistic studies revealed that the reaction underwent a quinine-catalyzed (3+2) cycloaddition, [3,3]-rearrangement, and intramolecular cyclization in a one-pot reaction and quinine catalyst played an important role on the intramolecular cyclization through hydrogen-bonding effect. The reaction was easily performed in gram scales and converted into various useful tricyclic building blocks. More importantly, the use of chiral quinine-derived squaramide as the catalyst, the angularly fused tricyclic isoxazolines containing five contiguous stereocenters can be obtained in excellent enantioselectivity (83%-93% ee) and diastereoselectivity (dr > 20:1).
- 1,3-Dipoles,
- Tricyclic compounds,
- Rearrangement,
- Cycloaddition,
- Nitrone,
- Nitroalkene,
- Isoxazoline
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